Buena Guía Sobre La Efectividad de Las InterTEACER26_Autism_Report_04!14!2011

8/10/2019 Buena Gua Sobre La Efectividad de Las InterTEACER26_Autism_Report_04!14!2011

1/906


2/906


3/906


4/906


5/906


6/906


7/906


8/906


9/906


10/906


11/906


12/906


13/906


14/906


15/906


16/906


17/906


18/906


19/906


20/906


21/906


22/906


23/906


24/906


25/906


26/906


27/906


28/906


29/906


30/906


31/906


32/906


33/906


34/906


35/906


36/906


37/906


38/906


39/906


40/906


41/906


42/906


43/906


44/906


45/906


46/906


47/906


48/906


49/906


50/906


51/906


52/906


53/906

19

Did not present aggregated results (i.e., included data for individual participants only) or presented graphical data only.

Literature Search and Retrieval Process Databases. We employed search strategies provided in Appendix A to retrieve research on thetreatment of autism spectrum disorders, including Asperger syndrome and PervasiveDevelopmental Disorder, Not-Otherwise-Specified. Our primary literature search employed thredatabases: MEDLINE via the PubMed interface, PsycINFO (psychology and psychiatryliterature), and the Education Resources Information Center (ERIC), searched from 1980 to the present. We also hand-searched the reference lists of all included articles to identify additionalstudies for review.

Grey literature. The AHRQ Scientific Resource Center also searched for information on thetwo medications specifically approved for treating irritability in ASDs (risperidone andaripiprazole) in resources including the websites of the US Food and Drug Administration andHealth Canada and clinical trials registries such as ClinicalTrials.gov. We gave manufacturers othese medications as well as of hyperbaric oxygen chambers an opportunity to provide additioninformation.

Search terms. Controlled vocabulary terms served as the foundation of our search in eachdatabase, complemented by additional keyword phrases to represent ASDs in the clinical andeducational literature. We also employed indexing terms when possible within each of thedatabases to exclude undesired publication types (e.g., reviews, case reports, news), items fromnon-peer-reviewed journals, and items published in languages other than English.

Our searches were executed between May 2009 and May 2010. Appendix A provides oursearch terms and the yield from each database.

Article selection process. Once we identified articles through the electronic database searches,review articles, and bibliographies, we examined abstracts of articles to determine whetherstudies met our criteria, including the cutoff date of the year 2000. Two reviewers separatelyevaluated each abstract for inclusion or exclusion, using an Abstract Review Form (AppendixB). If one reviewer concluded that the article could be eligible for the review based on theabstract, we retained it. The group included 3 expert clinicians (WS, ZW, JV), and two seniorhealth services researchers (MM, RJ). Two reviewers assessed the full text of each includedarticle using a standardized form (Appendix B); disagreements between reviewers were resolve by a third-party adjudicator.

Categorization of InterventionsAs has been previously noted, ASD intervention categories overlap substantially, and it is

difficult to cleanly identify the category into which an intervention should be placed.14 Weconsidered multiple approaches for organizing the results, and note that no alternativeapproaches would have changed our overall findings either in terms of outcomes or strength ofevidence for any category of intervention.

Behavioral interventions. We defined behavioral interventions to include early intensive behavioral and developmental interventions, social skills interventions, play/interaction-focused


54/906

20

interventions, interventions targeting symptoms commonly associated with ASDs such asanxiety, and other general behavioral approaches.

Early intensive behavioral and developmental interventions. We adopted a similar approach tothe operationalization of the early intensive behavioral and developmental intervention category

as Rogers and Vismara12

in their review of comprehensive evidence-based treatments for earlyASDs. Interventions in this category all have their basis in or draw from principles of applied behavior analysis (ABA), with differences in methods and setting. ABA is an umbrella termdescribing principles and techniques used in the assessment, treatment and prevention ofchallenging behaviors and the promotion of new desired behaviors. The goal of ABA is to teachnew skills, promote generalization of these skills, and reduce challenging behaviors withsystematic reinforcement. The principles and techniques of ABA existed for decades prior tospecific application and study within ASDs.

We include in this category two intensive manualized (i.e., have published treatment manualto facilitate replication) interventions: the University of California, Los Angeles (UCLA)/Lovaamodel and the Early Start Denver Model (ESDM). These two interventions have several key

differences in their theoretical frameworks and implementation, although they share substantialsimilarity in the frequent use of high intensity (many hours per week, one-on-one) instructionutilizing ABA techniques. They are described together here because of these similarities. Wenote, however, that the UCLA/Lovaas method relies heavily on one-on-one therapy sessionsduring which a trained therapist uses discrete trial teaching with a child to practice target skills,while ESDM blends ABA principles with developmental and relationship-based approaches foryoung children.

The other treatment approaches in this category also incorporate ABA principles, and may bintensive in nature, but often have not been manualized. We have classified these approaches broadly as UCLA/Lovaas-based given their similarity in approach to the Lovaas model. A third particular set of interventions included in this category are those using principles of ABA tofocus on key pivotal behaviors rather than global improvements. These approaches emphasize parent training as a modality for treatment delivery (e.g., Pivotal Response Training, HanenMore than Words, social pragmatic intervention, etc.) and may focus on specific behaviors suchas initiating or organizing activity or on core social communication skills. Because theyemphasize early training of parents of young children, they are reviewed in this category.

Social skills interventions. Social skills interventions focus on facilitating social interactions andmay include peer training and social stories.

Play/interaction-focused interventions. These approaches use interactions between children and parents or researchers to affect outcomes such as imitation or joint attention skills or the abilityof the child to engage in symbolic play.

Interventions focused on behaviors commonly associated with ASDs. These approaches attemptto ameliorate symptoms such as anger or anxiety, often present in ASDs, using techniques suchas Cognitive Behavioral Therapy (CBT) and parent training focused on challenging behaviors.


55/906

21

Additional behavioral interventions. We categorized approaches not cleanly fitting into the behavioral categories above in this group, which includes interventions such as sleep workshopand neurofeedback.

Educational interventions. Educational interventions are those focusing on improving

educational and cognitive skills and intended primarily to be administered in educationalsettings, or studies for which the educational arm was most clearly categorized. Theseinterventions include programs such as the Treatment and Education of Autistic andCommunication related handicapped CHildren (TEACCH) model and other treatmentsimplemented primarily in the educational setting. Some of the interventions implemented ineducational settings are based on principles of ABA and may be intensive in nature, but none ofthe educational interventions described in this report used the UCLA/Lovaas or ESDMmanualized treatments.

Medical and related interventions. We broadly defined medical and related interventions asthose that included the administration of external substances to the body in order to treat

symptoms of ASDs; medical interventions represented in the literature included in this reviewcomprised prescription medications, supplements and enzymes, diet therapies, and treatmentssuch as hyperbaric oxygen.

Allied health interventions. Allied health interventions included therapies typically provided byoccupational and physical therapists, including auditory and sensory integration, music therapyand language therapies.

Complementary and alternative medicine (CAM) interventions. Approaches in this categoryaddressed in this review include acupuncture and massage.

Literature Synthesis Development of Evidence Table and Data Abstraction Process

The staff members and clinical experts who conducted this review jointly developed theevidence table, which was used to abstract data from the studies. We designed the table to provide sufficient information to enable readers to understand the studies, including issues ofstudy design, descriptions of the study populations (for applicability), description of theintervention, appropriateness of comparison groups, and baseline and outcome data on construcof interest. We also abstracted data about harms or adverse effects of therapies, defined by theEPC program as the totality of all possible adverse consequences of an intervention.98

The team abstracted several articles into the evidence table and then reconvened as a group discuss the utility of the table design. We repeated this process through several iterations until wdecided that the table included the appropriate categories for gathering the information containein the articles. All team members shared the task of initially entering information into theevidence table. Another member of the team also reviewed the articles and edited all initial tablentries for accuracy, completeness, and consistency. The full research team met regularly duringthe article abstraction period and discussed global issues related to the data abstraction process.In addition to outcomes related to treatment effectiveness, we abstracted all data available on


56/906

22

harms. Harms encompass the full range of specific negative effects, including the narrowerdefinition of adverse events.

The final evidence table is presented in its entirety in Appendix C. Studies are presented inthe evidence table chronologically and alphabetically by the last name of the first author withineach year. When possible to identify, analyses resulting from the same study were grouped into

single entry. A list of abbreviations and acronyms used in the table appears at the end of thisreport.Several reporting conventions for describing studies in the evidence table were adopted that

warrant explanation, namely those related to practice setting, intervention setting, andassessments. We developed a brief taxonomy of the most common practice settings to reflect thentity that conducted the research. Practice settings include:

Academic (comprises academic medical centers and universities) Community Specialty treatment centers Residential centers Private practice Other (including pharmaceutical companies).We developed a similar listing for intervention settings to reflect where the intervention was

implemented, including home, school, clinic, and residential center. We considered the defaultsetting for drug studies to be the clinic (even if medication was provided by caregivers in thehome). Behavioral interventions involving the clinician in both the home and clinic were codedas occurring in both settings.

We captured data on the conduct of assessments in order to inform the evaluation of qualityof study conduct and to address questions of applicability of the intervention outcomes data todifferent populations of children with ASDs; data reported include the assessment conducted(e.g., ADOS), the context and administrator of the assessment (e.g., administered by study

psychologist in the clinic), and the timing (pre-intervention and at the six and eight week studyvisit, etc.).

Assessing Methodological Quality of Individual StudiesWe used a components approach to assessing the quality of individual studies, following

methods outlined in the EPC Methods Guide for Effectiveness and Comparative EffectivenessReviews.99 The individual quality components are described here. Individual quality assessmentsfor each study are reported in Appendix H.

In some instances, it was appropriate to apply specific questions only to one body ofliterature (e.g., to medical literature) and we note those cases where appropriate. Each domaindescribed below was assessed individually and combined for an overall quality level using thealgorithm below. Three levels were possible: good, fair, and poor.

Study design. Ideally, studies should use a comparison group in order to make causal inferences.The comparison group should accurately represent the characteristics of the intervention group the absence of the intervention. Specifically, factors that are likely to be associated with theintervention selected and with outcomes observed should be evenly distributed between groupsif possible. These factors may include, for example, age, intelligence quotient (IQ), or ASDseverity. Four questions were used to assess the study design:


57/906

23

1. Did the study employ a group design (have a comparison group)?2. Were the groups randomly assigned?3. If no, was there an appropriate comparison group?4. If yes, was randomization done correctly?

We considered the following elements in determining the appropriateness of a studysrandomization methods: Were random techniques like computer-generated, sequentiallynumbered opaque envelopes used? Were technically nonrandom techniques, like alternate daysof the week used? Was the similarity between groups documented?

Scoring: Studies with a group design were marked as minimally meeting this domain(+).Those that also received an affirmative response for either question three or four exceededthat minimum (++).

Diagnostic approach. We expected studies to accurately characterize participants, and in particular to ensure that study participants purported to be on the autism spectrum had beendiagnosed as such using a validated approach. We developed the hierarchy of diagnostic

approaches below to capture the method used; Table 7 includes more information about eachapproach.1. Was a valid diagnostic approach for ASDs used within the study, or were referred

participants diagnosed using a valid approach?A. A clinical diagnosis based on the DSM-IV, in addition to the ADI-R and ADOS

assessments.B. A clinical diagnosis based on the DSM-IV, in addition to either the ADI-R or ADOS

assessment.C. A combination of a DSM-IV clinical diagnosis with one other assessment tool from

Table 8; or the ADOS assessment in combination with one other assessment toolfrom Table 8.

D. Either a clinical DSM-IV-based diagnosis alone or the ADOS assessment alone.E. Neither a clinical DSM-IV-based diagnosis nor the ADOS assessment

Scoring: We classified diagnostic approaches A and B as gold standard (++), C and D asadequate (+) and E as unacceptable (-).

Table 7. Overview of diagnostic too ls used in quality sco ring hi erarchyDiagnostic instrument Overview

Autism DiagnosticObservation Schedule(ADOS)

Standardized, semi-structured observation-based review of social interaction, play,and communication for children and adults with suspected ASDs; consists of fourmodules appropriate for various language and developmental levels (nonverbal toverbally fluent) and administered directly to the individual by an examiner. Modulesprovide social/communication situations/activities designed to engage individuals and

elicit behaviors of interest. Does not currently provide scores related torestricted/repetitive behaviors so should be supplemented with additional diagnosticinformation.

Screening Tool for Autism in Two YearOlds (STAT)

Play and observation-based screening instrument designed to differentiate childrenwith autism from children with other developmental disorders once abnormaldevelopment has been indicated with an initial screening tool such as the M-CHAT;designed to be used with children between the ages of 24 to 35 months via a play-likeinteraction between the examiner and child; assesses behaviors related to imitation,play, communication/interaction, and joint attention.


58/906

24

Table 7. Overview of diagnostic tools used in quality sco ring hierarchy (continued) Diagnostic instrument Overview

Autism DiagnosticInterview-Revised (ADI-R)

Standardized, semi-structured clinical review administered by clinicians to caregiversof children or adults with suspected ASDs; focuses on behaviors in the domains/areasof social interaction, communication and language, and repetitive, restricted, andstereotyped behavior and interests. Scoring is based on the clinicians judgmentrelated to the caregivers responses regarding a subjects behavior; higher scores

indicate problematic behavior in a given domain, and scores align with diagnosticcriteria as outlined in the DSM-IV.Clinical interview basedon Diagnostic andStatistical Manual ofMental Disorders, 4thedition (DSM-IV)

DSM-IV articulates criteria for diagnosis of ASDs comprising impairments in the areasof social interaction; communication; restricted, repetitive, and stereotyped patterns ofbehavior, interests and activities; and delays in social interaction/communication andsymbolic or imaginative play. Clinical judgment of autistic symptomatology based onDSM-IV criteria is considered the gold standard of ASD diagnosis.

Childhood AutismRating Scale (CARS)

Behavioral observation- or caregiver report-based scale addressing over 10 domainstypically affected in autism (e.g., socialization, communication, emotionalresponsiveness) rated by the examiner on a 1 (age appropriate behavior) to 4(severely abnormal behavior) scale. Total scores under 30 do not indicate autism,scores of 30-36 reflect mild to moderate autism, and scores between 37 and 60indicate severe autism; intended to be used in concert with other instruments todiagnose ASDs.

Modified Checklist for Autism in Toddlers (M-CHAT)

Caregiver-reported checklist designed to screen for autism in children between theages of 16 and 30 months; includes items related to joint attention, social interests,imitation, responding to name.

Social CommunicationQuestionnaire (SCQ)

Caregiver-reported screening questionnaire designed to evaluate communication andsocial skills/functioning in children with suspected ASDs and determine the need forcomplete diagnostic evaluation; includes questions related to language and socialbehaviors--based on the ADI-R.

Social ResponsivenessScale (SRS)

Caregiver- or teacher- reported screening scale designed for use in children betweenthe ages of 4 and 18; generates scores related to cognitive, expressive, receptive, andmotivational aspects of social behavior in addition to autistic preoccupations; can beused to distinguish ASDs from other childhood psychiatric disorders.

Autism SpectrumScreeningQuestionnaire (ASSQ)

Screening instrument designed to be used with children between the ages of 7 to 16years; can be completed by teachers or caregivers. Addresses the domains of socialinteraction, communication, and restricted/repetitive behaviors considered to reflectbehavioral characteristics of children with ASDs, particularly higher functioning

individuals.Childhood AutismSpectrum Test (CAST)

Caregiver -reported screening tool designed for use in children between the ages of 4and 11, used particularly with higher functioning children; includes questions related tosocial skills, language, and repetitive behaviors and interests.

Participant ascertainment. The means by which participants enter the study cohort and areincluded in the analysis should be clearly described so that the reader can gauge the applicabilitof the research to other populations, and to identify selection and attrition bias. In this literatureit is important to understand the population in terms of characteristics commonly associated witoutcomes such as IQ, language and cognitive ability. We used four questions to assess participant ascertainment, including who was included in the analysis:

1. Was the sample clearly characterized (e.g., information provided to characterize

participants in terms of impairments associated with their ASDs, such as cognitive ordevelopmental level)?2. Were inclusion and exclusion criteria clearly stated?3. Do the authors report attrition?4. Were characteristics of the drop-out group evaluated for differences with the participant

group as a whole?


59/906

25

Scoring: Studies minimally had to have an affirmative answer for questions one or two ofthis domain to be adequate (+). Affirmative responses on questions three or four were consideresuperior (++).

Intervention characteristics. Sufficient detail should be provided on the intervention so that the

reader can fully understand the treatment and so that the research is potentially reproducible.This includes information on dosage, formulation, timing, duration, intensity and other qualitiesof the intervention. Furthermore, for behavioral treatments there should be some assurance thatthe treatment providers stayed true to the treatment process (fidelity) and for medical treatment,there should be some assurance that participants adhered to their medication or that adherencewas accounted for. Furthermore, because other treatments occurring simultaneously with thetreatment under study could have substantial impact on outcomes, it is important that authorsgather data on treatments being obtained by their participants outside of the study. We used threquestions to obtain quality information in this domain, and allowed for the interventiondescription to be provided in another, referenced paper:

1. Was the intervention fully described?

2. Was treatment fidelity monitored in a systematic way? (for non-medical interventions)3. Did the authors measure and report adherence to the intended treatment process? (formedical interventions)

4. Did the authors report differences in or hold steady all concomitant interventions?

Scoring: Authors needed to fully describe the intervention for the study to be awarded one point (+), and studies were given an additional point (++) if they also reported on or held steadyconcomitant interventions and monitored either fidelity or adherence.

Outcomes measurement. The ASD literature reviewed for this report included more than 100outcome measures. To understand the meaning of the results at hand, readers need to beconfident that the measure validly assessed the intended target behavior or symptom. It is alsoimportant that authors specifya priori what their outcome of primary interest is as the rest of thestudy, including sample size, should derive from the intent to measure this outcome. Finally, inmeasuring outcomes, the individual responsible for coding or measuring effect should be blindeto what intervention the participant received. We attempted to use three questions for thisdomain, but were forced to drop one regarding whether primary outcomes were pre-determinedas it was almost uniformly impossible to tell whether authors had a called shot ora priori primary outcome, or to tell which of several outcomes was the primary one. We were left withtwo questions:

1. Did outcome measures demonstrate adequate reliability and validity (including inter-observer reliability for behavior observation coding)?

2. Were outcomes coded and assessed by individuals blinded to the intervention status ofthe participants?

Scoring: To meet the requirement for an adequate score on outcomes measurement (+),studies were required to have an affirmative answer to both questions.

Statistical analysis. Studies could either have appropriate or inappropriate analysis. We used aseries of questions to guide the determination:


60/906

26

1. For RCTs, was there an intent-to-treat analysis?2. For negative studies, was a power calculation provided?3. For observational studies, were potential confounders and effect measure modifiers

captured?4. For observational studies, were potential confounders and effect measure modifiers

handled appropriately?Confounders are variables that are associated both with the intervention and the outcome an

that change the relationship of the intervention to the outcome. These are variables that we woucontrol for in analysis. Effect measure modifiers are variables that we think of as stratifying, inthat the relationship between the intervention and outcome is fundamentally different in differenstrata of the effect modifier. Observational research should include an assessment of potentialconfounders and modifiers, and if they are observed, analysis should control for or stratify onthem. Other considerations included: was the candidate variable selection discussed/noted?, wathe model-building approach described? Were any variables unrelated to the studied variablesthat could have altered the outcome handled appropriately? Were any variables not under study

that affected the causal factors handled appropriately? Was the candidate variable selectiondiscussed/noted?Scoring: Studies needed a yes or not applicable (NA) on each of the analysis questions to

receive a point (+) for analysis.Scores were calculated first by domain and then summed and weighted as described in Table

8 to determine overall study quality (internal validity).

Table 8. Quality scorin g algorit hmDefinition and scoring algorithm RatingScore algorithm for internal validity quality rating 8/10 points, including a ++ on study design and ++ on diagnostic approach Good quality 6/10 points, including at least a + on intervention Fair quality 5/10 points or less Poor quality

Applicability. Finally, it is important to consider the ability of the outcomes observed to apply both to other populations and to other settings (especially for those therapies that take placewithin a clinical/treatment setting but are hoped to change behavior overall). Our assessment ofapplicability took place in three steps. First, we determined the population, intervention,comparator, and setting (PICOS) in each study and developed an overview of these elements foeach intervention category (Appendix I). Second, we reviewed potential modifiers of effect oftreatment to identify subgroups for which treatments may be effective, and finally, we answeredthe following three questions:

1. Were outcomes measured in at least one context outside of the treatment setting?

2. Were outcomes measured in natural environments to assess generalization?3. Considerations: Was an assessment conducted in the home, school, or communitysettings (i.e., a setting a child typically goes to in an ordinary week)?

4. Were followup measures of outcome conducted to assess maintenance of skills at least 3months after the end of treatment?


61/906

27

These ratings of applicability do not factor into a studys overall quality score (good, fair, or poor), nor are they part of strength of evidence. Rather they are presented separately and arediscussed in Chapter 4.

Strength of Available EvidenceThe assessment of the literature is done by considering both the observed effectiveness ofinterventions and the confidence that we have in the stability of those effects in the face of futur

research. The degree of confidence that the observed effect of an intervention is unlikely tochange is presented as strength of evidence, and it can be regarded as insufficient, low, moderator high. Strength of evidence describes the adequacy of the current research, both in terms ofquantity and quality, as well as the degree to which the entire body of current research providesconsistent and precise estimate of effect. Interventions that have demonstrated benefit in a smalnumber of studies but have not yet been replicated using the most rigorous study designs willtherefore have insufficient or low strength of evidence to describe the body of research. Futureresearch may find that the intervention is either effective or ineffective.

Methods for applying strength of evidence assessments are established in the Evidence-basePractice Centers Methods Guide for Effectiveness and Comparative Effectiveness Reviews

99 and are based on consideration of four domains: risk of bias, consistency in direction of the

effect, directness in measuring intended outcomes, and precision of effect. Strength of evidenceis assessed separately for major intervention-outcome pairs. We also required at least 3 fairstudies to be available to assign a low strength of evidence rather than considering it to beinsufficient. For determining the strength of evidence for effectiveness outcomes, we onlyassessed the body of literature deriving from studies that included comparison groups. Werequired at least one good study for moderate strength of evidence and two good studies for higstrength of evidence. In addition, to be considered moderate or higher, intervention-outcome pairs needed a positive response on two out of the three domains other than risk of bias.

For determining the strength of evidence related to harms, we also considered data from cas

series. Once we had established the maximum strength of evidence possible based upon thesecriteria, we assessed the number of studies and range of study designs for a given intervention-outcome pair, and downgraded the rating when the cumulative evidence was not sufficient to justify the higher rating. The possible grades were:

High: High confidence that the evidence reflects the true effect. Further research isunlikely to change estimates.

Moderate: Moderate confidence that the evidence reflects the true effect. Further researchmay change our confidence in the estimate of effect and may change the estimate.

Low: Low confidence that the evidence reflects the true effect. Further research is likelyto change confidence in the estimate of effect and is also likely to change the estimate.

Insufficient: Evidence is either unavailable or does not permit a conclusion.


62/906

28

ResultsChapter 3 presents the results of our systematic review. Each category of intervention

includes first an overview of the content of the literature as a whole, including the range of studydesigns used, outcomes assessed and participants included. The summary of the literature provides further discussion and analysis, focusing primarily on those studies that received eithea good or fair quality rating. Overview tables document the interventions included, availability literature by study design, diagnostic approaches, timing of final outcome assessments,geographic location of study populations, and final numbers of participants with autism spectrudisorders (ASDs) for each intervention section (Tables 9, 14, 16, 23, 25).

Studies that received a good or fair quality rating and include a comparison group(randomized controlled trial (RCT), controlled trial, or prospective or retrospective cohort studyalso are described in more detailed summary tables in the relevant section of text. Forinformation on studies not included in the summary tables, please see the evidence table inAppendix C; for information on quality scores for each study, see Appendix H.

Ar ticle SelectionOf the entire group of 4,120 citations, 714 required full text review (Figure 2). For the full

article review, two reviewers read each article and decided whether it met our inclusion criteria,using a Full Text Inclusion/Exclusion form. Of the 714 full text articles reviewed, we retained183 papers (comprising 159 unique studies) and excluded 531 papers. Reasons for articleexclusion are listed in Appendix D.


63/906

29

Figure 2. Disposi tion of articles addressing therapies for chil dren with ASDs

KQ1. Effects of Treatment on Core and Commonly Associated Symptomsin Children With ASDs: Behavioral Interventions

A wide range of interventions can be classified as behavioral. For this review, we includedstudies of early intensive behavioral and developmental interventions, which comprisedUniversity of California, Los Angeles (UCLA)/Lovaas-based approaches, the Early Start DenveModel (ESDM), and parent training approaches incorporating principles of Applied BehaviorAnalysis (ABA) to improve outcomes among young children with ASDs; social skillsinterventions; focal play-based /interaction-based interventions; behavioral interventions focuseon associated behaviors; and a small group of other behavioral interventions assessing otherinterventions in core/associated areas (e.g., sleep workshops). Table 9 summarizes criticalaspects of all studies of behavioral interventions, those addressing key question (KQ) 1 as well behavioral studies discussed in the KQ2 and KQ7 sections of the report.

aThe total number of articles in the exclusion categories exceeds the number of articles excluded because most of thearticles fit into multiple exclusion categories; KQ=key question

Non-duplicate articlesidentified in searches

n = 4,120

Literature search: n = 3,779 Hand search/ grey literature

search: n = 341

Full text articlesreviewed

n=714

Articles excludedn=3,406

Full text articles excluded

n = 531 a

Participants not within age rangen = 293

Not original researchn = 135

Ineligible study sizen = 406

Irrelevant to key questionsn = 285

Unable to abstract datan = 16Unique full text

articles included inreview

n=183 (comprising159 unique

studies)

154 KQ138 KQ24 KQ3

1 KQ417 KQ50 KQ64 KQ7


64/906

30

Table 9. Overview of behavior al studi es a

Characteristic R C T s

n R C T s

P r o s p e c

t i v e

c o h o r t s

t u d i e s

R e t r o s p e c

t i v e

c o h o r t s

t u d i e s

P r o s p e c

t i v e

c a s e s e r i e s

R e t r o s p e c

t i v e

c a s e s e r i e s

T o t a l L i t e r a

t u r e

(n=29) (n=7) (n=6) (n=3) (n=25) (n=8) (n=78)

Intervention

Early intensive behavioral anddevelopmental

6 5 5 2 11 6 35

Social skills 8 0 0 1 7 0 16Play-/interaction-based 7 0 0 0 4 2 13

Interventions targeting associatedbehaviors

7 1 1 0 2 0 11

Other 1 1 0 0 1 0 3

Diagnostic approach Clinical DSM-IV dx +ADI-R and/or

ADOS 5 0 2 0 9 0 16

Combination approaches b 15 2 3 0 10 4 34No DSM-IV or ADOS dx /

unspecified9 5 1 3 6 4 28

Treatment duratio n

1 to 3 months 13 3 1 0 5 0 22 >3 to 6 months 5 1 0 0 4 0 10

>6 to 12 months 4 1 2 0 9 2 18

>12 months 3 2 3 3 3 5 19

Unknown/not reported 0 0 0 0 2 1 3 Study population

U.S. 16 3 2 1 17 4 43Europe 5 4 1 2 3 2 17

Asia 0 0 0 0 0 0 0Other 8 0 3 0 5 2 18

Total N partici pants 1,265 215 254 157 860 529 3,065ADI-R=Autism Diagnostic Interview-Revised; ADOS=Autism Diagnostic Observation Schedule; DSM-IV=Diagnostic andStatistical Manual of Mental Disorders, 4th edition; dx=diagnosis; nRCT=non randomized controlled trial; RCT=randomized

controlled trialaThis table provides an overview of selected data for all studies categorized as behavioral; not all behavioral studies are addressein the KQ1 section. Some behavioral studies apply only to KQ2 and KQ7; however these studies are included in this table to provide a comprehensive overview of available behavioral literature. The numbers in the table indicate the number of uniquestudies with each characteristic. bClinical DSM-IV dx +other diagnostic tool or ADOS + other diagnostic tool or only clinical DSM-IV dx or only ADOS.

Early Intensive Behavioral and Developmental Interventions Early intensive behavioral and developmental interventions include interventions based on:


65/906

31

ABA-based approaches including the UCLA/Lovaas method and variants, naturalistic/developmental principles (i.e., ESDM) parent/family-based training (e.g., Pivotal Response Training, Hanen More Than Words,

and social communication training).

We adopted a similar approach to the operationalization of this category as Rogers andVismara12 in their review of comprehensive evidence-based treatments for early ASDs.Interventions in this category all have their basis in or draw from principles of applied behavioranalysis (ABA), with differences in methods and setting. ABA is an umbrella term describing principles and techniques used in the assessment, treatment and prevention of challenging behaviors and the promotion of new desired behaviors. The goal of ABA is to teach new skills, promote generalization of these skills, and reduce challenging behaviors with systematicreinforcement. The principles and techniques of ABA existed for decades prior to specificapplication and study within ASDs.

We include in this category two intensive manualized (i.e., have published treatment manualto facilitate replication) interventions: the UCLA/Lovaas model and the ESDM. These two

interventions have several key differences in their theoretical framework and implementation,although they are similar in the use of high intensity (many hours per week, one-on-one)instruction utilizing ABA techniques. The UCLA/Lovaas method relies heavily on one-on-onetherapy sessions during which a trained therapist uses discrete trial teaching with a child to practice target skills, while the ESDMblends ABA principles with developmental andrelationship-based approaches for young children.

The other treatment approaches in this section also incorporate ABA principles, and may beintensive in nature, but have not been manualized. We have classified these approaches broadlyas UCLA/Lovaas-based given their similarity in approach to the Lovaas model. A third set ofinterventions included here are those using the principles of ABA to focus on key pivotal behaviors rather than global improvements. These approaches emphasize parent training (e.g.,

Pivotal Response Training, Hanen More than Words, social pragmatic intervention, etc.) andmay focus on specific behaviors such as initiating or organizing activity or on core socialcommunication skills. Because they emphasize early training of parents of young children, theyare reviewed here.

We review the results of UCLA/Lovaas-based approaches and parent training approachesfocused on pivotal behaviors below; we discuss results of the ESDM in the KQ7 section of thereport given the questions focus on younger children.

Studies focusing on one specific targeted outcome area (e.g., social skills, maladaptive behavior, mental health comorbidities, play) and intervention studies delivered primarily viaeducational protocols or allied health providers are reviewed in other sections of this report.

Content of the literature. We identified 34 papers100-133

from 30 unique study populations thataddressed early intensive behavioral and developmental interventions. A majority of thereviewed literature examined specific early intensive behavioral and developmental approacheswith most using variants of the UCLA/Lovaas model or other ABA-based approaches.101-107,110,111,113-115,118,121,122,124-127,129-133

Four papers evaluated various parent trainings aimed at social communicationskills,100,108,109,128 two papers examined Pivotal Response Training,117,120 two studies examinedand described eclectic approaches112,119,123 and one study examined a parent training blending


66/906

32

Pivotal Response Training and other behavioral approaches (Group Intensive FamilyTraining).116

Summary of the literature. Of the 34 papers in this section100-130 comprising 30 unique studies,11 were fair, and 19 were poor. Outcomes of RCTs and cohort studies rated fair in quality are

summarized in Table 10.Studies of UCLA/Lovaas-based approaches . The one RCT on the UCLA/Lovaas treatment thatmet inclusion criteria had fair quality.114 This study compared a clinic-based method to a parent program, and targeted children at about 36 months of age. The study114 was the first attemptedreplication of Lovaas manualized intervention to use random assignment, a standardizedassessment battery, and explicit accounting of intervention hours. It included 28 children with amean intelligence quotient (IQ) of 51 randomized to either an intensive treatment group(UCLA/Lovaas model with an average of 25 hours per week of individual treatment per yearwith reduced intervention over next 1 to2 years) or a parent-training group (3-9 months of parentraining). Gains in IQ were much more tempered than that of Lovaas original noncontrolled

study.21

Children in the treatment group gained a mean of 15 IQ points in comparison to therelatively stable cognitive functioning of the control group, although average IQ in the treatmengroup remained in the impaired range. Most of the children who demonstrated large gains in IQwere within the subgroup diagnosed with Pervasive Development Disorder-Not OtherwiseSpecified (PDD-NOS), whereas children with classically defined Autistic Disorder demonstratemodest improvements.

Two children in the experimental group (vs. one in the control) achieved the best outcomeor recovery status previously defined by Lovaas. No post-treatment group differences wereseen in adaptive behavior or challenging behavior. Thus, while replicating improvements incognitive ability for some children with ASDs within the repeated discrete trial teaching inherento UCLA/Lovaas method, the study in fact demonstrated a less dramatic impact for the population of children for whom this approach is often recommended (i.e., children withclassically defined Autistic Disorder) compared with what was previously reported.

Seven prospective cohort studies and nonrandomized trials were available on UCLA/Lovaas based methodologies, but none made the same comparisons either in terms of interventions or populations. Hayward and colleagues126,132 examined the progress of children receiving eitherintensive clinic directed UCLA/Lovaas-based intervention (n=23; mean age=36 months; 37hours of weekly treatment) or an intensive parent-managed model (n=23; mean age=34 months34 hours of weekly treatment) over the course of one year in the United Kingdom. Groupassignment was based solely on geographic location. At follow up, both groups had improvedsignificantly in IQ (16 point gain), nonverbal IQ (10 points), language use/understanding, andmost areas of adaptive functioning with the exception of daily living skills but there were nodifferences between the groups.

Two studies compared intensive center-based treatment to community care. Howard andcolleagues129 studied preschool-aged children receiving intensive behavior analytic treatment(n=29, 1:1 treatment for 25-40 hours per week), intensive eclectic intervention (n =16, higherteacher-student ratio intervention for approximately 30 hours per week), and children receivinggeneral intervention in public early intervention programs (n=16, combined methods, smallgroups, 15 hours per week). Groups were assigned via educational placement teams thatspecifically included parent input. Controlling for age at diagnosis and combined parental


67/906

33

education, children in the intensive behavior analytic group demonstrated significantimprovements in all areas assessed at followup, including an average IQ of 89 (41-pointimprovement over baseline) and a 24-point difference from the combined mean of the otherintervention groups.

Significant differences between the eclectic and generic intervention groups were not presen

at followup. Findings do suggest substantial improvement via an intensive approach for youngchildren with autism; however, important differences in group assignment at baseline, difficultiewith systematic measurement overtime, the lack of reported treatment fidelity or adherencecharacteristics, and the small number of children in the comparison group limits theinterpretation of these findings.

These results were echoed in another study105 of 42 children in which those receiving theLovaas program had significantly higher IQs (mean=87, gain of 25; mean=73, 14 points) andadaptive behavior skills at outcome, compared with children in undefined community care.Receptive language improvements were observed but were not significant, and expressivelanguage skills and socialization scores on the Vineland Adaptive Behavior Scale (VABS) werenot different for the two groups at year 3 outcome. Twelve of the 21 children in the behavioral

group had IQs >85 compared with 7 of 21 in the eclectic treatment group at outcome. Likewisemore children in the Lovaas group were in typical schools subsequent to intervention (17 vs. 1)although this specific outcome is potentially attributable to a wide variety of factors includingsome that might correlate with differences in socioeconomic status and family constellationevident between the groups.

One study125 of two centers compared an eclectic approach (including the Developmental,Individual-Difference, Relationship-Based/Floortime model, Treatment and Education ofAutistic and Communication related handicapped CHildren (TEACCH) and ABA-basedapproaches) to UCLA/Lovaas-based intervention alone. Hours spent in the intervention wereconsistent at 8 hours per day, and children were assessed over one year. Significant groupdifferences were noted in terms of both language/communication and reciprocal socialinteraction domain scores on the Autism Diagnostic Observation Schedule (ADOS), with bothgroups showing decreases in symptom tallies but more substantial decreases in the ABA group. No significant differences in IQ change were reported. While demonstrating impact on certainADOS symptom scores, these changes were small, and more recent approaches suggest thatcalculating an ASD severity score may be a more valuable and sensitive way for measuringchanges in ASD symptoms in response to intervention.134 In a subsequent study on diagnosticstability124 with unclear sample overlap, most children receiving intervention continued todisplay scores in the ASDs range on the ADOS (n=53) although some childrens classificationdid shift.

Finally, one study tried to assess the role of intensity of the intervention on outcomes. Reedand colleagues103 studied the effectiveness of varying intensity of home-based Lovaas-based programs offering primarily one-to-one teaching. High intensity interventions (n=14) weredefined as those provided for an average of 30 hours per week. Low intensity interventions(n=13) were provided for on average 13 hours per week. Assignment to the particularintervention modality was based on geographic location, and children in the high intensity grouhad higher ability and cognitive scores and lower autism severity scores at baseline. Childrenwere assessed 9-10 months after initiation of intervention. Children receiving high intensityintervention demonstrated statistically significant improvements in intellectual and educationalfunctioning from baseline. Children receiving low intensity intervention demonstrated


68/906

34

statistically significant changes in educational functioning and nonsignificant improvement incognitive functioning. The only significant difference between the groups was in improvededucational functioning associated with high intensity interventions. No group differences werefound in autism severity, cognitive functioning, or adaptive behavior functioning.

Three additional cohort studies101,106,130 of UCLA/Lovaas-based methodologies provided

inconsistent data on the benefit of behavioral approaches, but all three had substantial risk of biand were thereby rated as poor quality in this report. Nonetheless, they suggest that behavioralapproaches may have promise for bolstering aspects of cognitive, language and adaptivefunctioning in preschool children with ASDs.

Case series of early intervention approaches104,113,118,119,131 had mixed results, likely in partdue to the substantial heterogeneity of interventions examined even within individual studies,little or no control of concomitant interventions, and poor fidelity to any given approach.Outcomes in these studies were more likely to be parent-reported and not based on validatedtools.

Several chart reviews and other retrospective analyses have been used to understandtreatment patterns and effects.111,112,115,121-123 Interpretation of findings is most appropriately

confined to noting that some children receiving intervention have displayed improvementsduring intervention in cognitive, adaptive, and autism-specific impairments, that characteristicsof starting treatment and baseline abilities are correlated with improvement in some instances,and heterogeneity in terms of improvement is quite common. We do not describe these studieshere, but details on all of them are available in the evidence table in Appendix C.

One chart review,122 however, does provide some evidence for the feasibility of providingintensive behavioral interventions on a larger scale as it reviews data on 322 children served in large service catchment area. Given the methodological limits including lack of a clearly defineintervention characteristics/protocol, lack of a comparison group, retrospective collection, andlack of key measures for certain children at certain times, the intervention results are limited.However, the study suggests the feasibility of providing intensive intervention to a large group ochildren.

Studies of intensive parent training approaches . Of the seven studies100,108,109,116,117,120,128 on parent training, four 100,108,109,120 included comparison groups and had fair 100,108,109 or poor 120 quality. Three were RCTs,100,108,109 including one pilot study108 with a report of a laterimplementation of the intervention including different participants.100 Drew et al.109 comparedthe effects of a home-based, parent-delivered intervention aimed at improving socialcommunication and managing challenging behavior for 12 children with ASDs with acommunity-based control intervention group of 12 children (mean age 23 months at start oftreatment).

Components of the interventions for social communication included developing jointattention, teaching routines, and play activities promoting interaction. Reinforcement techniqueincluding for alternative behaviors, were used to address challenging behaviors. Training wasconducted at home visits (3 hours weekly for 6 weeks), with parents asked to engage inintervention activities for a half to1 hour daily. One year after treatment initiation, the parenttraining group reported that their children used more words than the community group. Therewere no group differences on nonverbal intelligence quotient (NVIQ), autism symptom severityor words/gestures observed during followup assessment. Unexpectedly, the treatment group lostIQ points during the study; whereas the control group demonstrated relatively stable cognitive


69/906

35

abilities. This finding is further confounded by a significantly higher IQ present in the treatmengroup at initiation of the study.

Aldred et al.108 compared a parent-based intervention focused on advancing socialcommunication skills within interactions (n = 14, median age 51 months) to treatment as usual(n=14, median age 48 months). Parents participated in initial workshops, monthly intervention

sessions where videotaped interactions were reviewed, and 6 months of maintenance visits(approximately once every 2 months). Twelve months after baseline, blinded evaluations showeimprovements on ADOS scores, with substantial improvement within the social domain,increased expressive vocabulary, as well as improved communication-related behaviors codedduring interactions. Language gains were most prominent in younger, lower-functioningchildren. A lack of standardized measures of developmental performance, including baselinecognitive skills, as well as challenges in understanding and defining treatment as usual limitinterpretation of the findings.

In a report of a later intervention of this model, 152 children between the ages of 2 and 4years were randomized to treatment as usual or treatment as usual plus parent training in socialcommunication.100 Time in treatment as usual interventions was similar across groups as were

the types of interventions employed. Similar numbers of children in both groups experienceddiagnostic shifts from core autism to other diagnoses on the ASDs spectrum as diagnosed on theADOS-G. Teacher ratings of language and communication after intervention were notsignificantly different between groups, though ratings of parent-child interactions by independeassessors were positive for children in the social communication group. Parent ratings oflanguage and social communication were also more positive for the social communication grou

Stahmer and Gist120 examined the effects of an explicit parent education support group with a parent education program focusing on Pivotal Response Training, a treatment program designedto enhance core skill areas in autism using naturalistic interactions. Parents met with theintervention provider weekly for 12 weeks and were taught techniques for presenting clearinstructions, following and supplementing child choice, and providing direct/naturalisticreinforcement. Involvement in the 12-week intervention was successful in changing parentingtechniques and perceived language gain. However, the lack of randomization, wide variation inchildren served, the lack of objectively assessed changes in child behavior, and the small numbeof participating limit the reported results.

Table 10. Outcom es of early int ensive behavioral and developmental int erventions Aut ho r, year , countr y

Groups, N enrollment/Nfinal

Study quality

Age, mean (m onths) SDIQ, mean SD

Key outcomes

UCLA/Lovaas-based appr oachesHayward et al. , 2009, UK

G1: Intensive clinic-basedUCLA/Lovaas-basedintervention, 23/20G2: Intensive parent-managed treatment, 21/19

Quality: Fair

G1: 35.7 6.2G2: 34.4 5.7

NR

No significant group differences at followup. Improvements in both groups in IQ, non-verbal IQ,

language use/understanding, and most areas ofadaptive functioning, with the exception of dailyliving skills.


70/906

36

Table 10. Outcomes of early intensiv e behavior al and developmental interventions (continu ed) Aut ho r, year , countr y


Study quality

Age, mean (months) SDIQ, mean SD

Key outcomes

UCLA/Lovaas-based appr oaches

Reed et al.2007, UK

G1: High intensityintervention, 14/14G1a: High intensity withfocus on Lovaastechniques, 4/4G1b: High intensity withfocus on verbal behavior,5/5G1c: High intensity withfocus on CABAS methods,5/5G2: Low intensityintervention in home-baseddirect teaching sessions,13/13

Quality: Fair

G1: 42.9 (14.8)G1a: 47.5 (13.5)G1b: 38.0 (9.9)G1c: 44.2 (20.5)G2 : 40.8 (5.6)

NR

Children in the high intensity group had higherability and cognitive scores and lower autismseverity scores at baseline.

G1: statistically significant improvements inintellectual and educational functioning frombaseline.

G2: statistically significant changes in educationalfunctioning.

Group comparisons showed educationalfunctioning improvements for G1 compared withG2.

No group differences were found in autismseverity, cognitive functioning, or adaptivebehavior functioning.

Zachor et al. 2007, Israel

G1: UCLA/Lovaas-basedintervention, 53/53G2: Eclectic approach,15/15

Quality: Fair

G1: 25.1 3.8G2: 26.3 4.6

NR

No baseline differences in terms of familycharacteristics or child functioning.

Significant time by intervention effects noted in ADOS language/communication and reciprocalsocial interaction domain scores--more substantialdecreases in the UCLA/Lovaas group.

Following intervention both groups showedimprovements in cognitive and verbal scores andadaptive behavior skills.

Cohen et al.1

2006, US

G1: UCLA/Lovaas-basedintervention, 21/21G2: Local services, 21/21

Quality: Fair

G1: 30.2 5.8G2: 33.2 3.7

G1: 61.6 16.4G2: 59.4 14.7

Significantly higher IQs and adaptive behaviorskills post-treatment in G1. Receptive language improvements noted at 3

years, but expressive language skills andsocialization scores were not different for the twogroups.

Twelve of 21 in the behavioral group had IQs >85compared with 7 of 21 in the eclectic treatmentgroup.

Howard et al. 1 2005, US

G1: UCLA/Lovaas-basedintervention, 37/29G2: Intensive eclectictherapyG3: Non-intensive eclectictherapyG2+G3: 41/32

Quality: Fair

At intake:G1: 30.86 5.16G2: 37.44 5.68G3: 34.56 6.53

At followup:G1: 45.66 6.24G2: 50.69 5.64G3: 49.25 6.81

G1: 58.84 18.15G2: 53.69 13.50G3: 59.88 14.85

G1: significant improvements in all areas assessedat followup, including average IQ of 89(representing a 41 pt improvement over baselineand a 24 pt improvement over the combined meanof the other intervention groups).


71/906

37

Table 10. Outcomes of early intensiv e behavior al and developmental interventions (continu ed) Aut ho r, year , countr y


Study quality

Age, mean (months) SDIQ, mean SD

Key outcomes

Eikeseth et al. , 2002, Norway

G1: UCLA/Lovaas-basedintervention, 13/13G2: Eclectic therapy, 12/12

Quality: Fair

G1: 66.31 11.31G2: 65 10.95

G1: 61.92 11.31G2: 65.17 14.97

Analysis of change scores demonstrated moreimprovement for G1 regarding IQ and language.

G2 scores were higher at baseline across mostareas of measurement compared with G1.

Smith et al. 11 2000, US

G1: UCLA/Lovaas-basedintervention, 15/15G2: Parent training fromLovaas manual, 13/13

Quality: Fair

Intake:G1: 36.07 6.00G2: 35.77 5.77Followup:G1: 94.07 13.07G2: 92.23 17.24

G1: 50.53 11.18G2: 50.69 13.88

G1 gained mean of 15 IQ pts compared withrelatively stable cognitive functioning of controls.

Significant improvement for G1 in visual-spatialskills and expressive language.

IQ scores averaged in impaired range at outcomefor G1 and PDD-NOS children appeared toaccount for majority of change.

No post-treatment group differences seen foradaptive or challenging behavior.Parent training

Aldred et al. 1 2004, UK

G1: Parent training insocial communicationintervention pluscommunity intervention,14/14G2: Communityintervention, 14/14

Quality: Fair

G1: median 48 moG2: median 51 mo

NR

G1 showed improvements in ADOS scores, socialinteraction, expressive language, childcommunication acts during interaction.

No adaptive behavior differences or differences inparenting stress between groups.

Language gains particularly prominent in younger,lower functioning children.

Drew et al. 1 2002, UK

G1: Parent training, 12/12G2: Local/eclectic services,12/12

Quality: Fair

Intake:G1: 21.4 2.7G2: 23.6 3.8

Followup:G1: 33.5 2.5G2: 36.2 4.5

G1: 88.1 11.2 (NVIQ)G2: 23.6 3.8 (NVIQ)

At 12 mo, G1 had more words and a trend towardunderstanding more words than G2.

No group differences on NVIQ, autism symptomseverity, parental report of stress, or words orgestures produced during followup assessment.

ABA=applied behavior analysis; ADI=Autism Diagnostic Interview; ADOS=Autism Diagnostic Observation Schedule;ASDs=autism spectrum disorders; G=group; IQ=intelligence quotient; mo=month; N=number; NVIQ=nonverbal intelligencequotient; PDD-NOS=Pervasive Development Disorder-Not Otherwise Specified; RBS=Repetitive Behavior Scale; SD=standarddeviation; UCLA=University of California, Los Angeles; UK=United Kingdom; VABS=Vineland Adaptive Behavior Scale

Social Skills Interventions The social interventions reviewed in this section focus primarily on children at elementary-

school ages and those functioning at higher cognitive/developmental levels. They use variousapproaches to address three primary dimensions of social competence: specific behavioral skills(e.g., greetings, initiating game play, joint attention), affective understanding (e.g., recognizingemotions in self and others), and social cognition (e.g., theory of mind, problem-solving, self-regulation).


72/906

38

Content of the literature. We located 16 unique papers addressing social skills interventions.This number includes two sets of papers with possibly overlapping samples evaluating aSkillstreaming intervention135,136 and a cognitive-behavioral-ecological social skillsapproach.137,138 The ages of children studied ranged from 4-16 years old. Twelve studies focused

exclusively on higher functioning children or included language and/or cognitive requirementsamong their eligibility criteria.135-146 Three studies provided individual treatment tochildren,137,145,147 three used a combination of individual and small group formats,138,146,148 andnine employed a small group format only.135,136,139-144,149 In addition, five interventions includedsome form of parent training or involvement as an adjunct to child treatment.137,139,141,144,146 Forthe 14 studies with prospective designs, the total amount of training provided ranged from 6.7hours to 180 hours. Table 10 summarizes additional details.

Among studies of social skills interventions, seven were fair quality and nine were poor.

Summary of the literature. Three RCTs139,141,146 (Table 11) evaluated social skills interventionstargeting high functioning children with ASDs using a format that involved training for both

children and their parents. The criteria for determining whether a child was high functioning antherefore eligible to participate varied by study, but at a minimum the child had to have a verbalIQ above 60. Different outcome measures were used across the samples, making directcomparisons difficult.

The Childrens Friendship Training141 program involves children with and without ASDs,and uses didactic instruction on rules of social behavior; modeling, coached behavioral rehearsaand performance feedback during treatment sessions; rehearsal at home; homework assignmentand coaching by parents during play dates with a peer. Children were randomly assigned toreceive Childrens Friendship Training either immediately or 12 weeks later (Delayed TreatmenControl group). Treatment was conducted in 60-minute small parallel group sessions for parentsand children, and lasted 12 weeks.

Immediately following treatment, the Childrens Friendship Training group showedsignificant improvements in social behavior and social cognition compared with the DelayedTreatment Control group. Children in the treatment group also spent less time during the playdate engaged in minimally socially interactive activities (such as watching television) comparedwith the delayed treatment group (p


73/906

39

forecast behavior; perspective taking; executive functioning, which allows for planning andabstract thinking; problem solving; and conversation skills. Eighteen boys between 8 and 12years old met eligibility criteria.139

Participants were matched on age and IQ and randomly assigned to an immediateintervention condition or a wait list condition. Parents and children in the treatment condition

received the Social Adjustment Enhancement Curriculum at a clinic for 20 weekly 1.5 hoursessions. Children and parents met separately. Child groups of four or five were structured withhigh adult-to-child ratio and followed a consistent schedule each week, using a variety ofinstructional strategies including in vivo teaching, visual templates, games, and role playing.

Immediately following the intervention participants in Social Adjustment EnhancementCurriculum had higher facial recognition scores post-treatment (p


74/906

40

general feedback and noncontingent rewards). The only difference found between the responsecost and noncategorical feedback intervention conditions post-treatment was that interventionisreported significant improvements measures of atypicality, withdrawal, and behavior symptomsin the response cost group relative to the noncategorical feedback group (p


75/906

41

interaction with peers; outcome measures were generally parent-reported. The studies also lackecontrol groups so it is difficult to determine whether improvements are treatment-specific.

Table 11. Outcomes of RCTs of social ski lls behavioral in terventions Author , year, cou ntry

Groups, N enrollment/N

finalStudy quality

Age, mean years SDIQ, mean SD

Key outcomes

Quirmbach et al.2009, US

G1: Social Stories, standardcondition, 15/15G2: Social stories, directivecondition, 15/15G3: Control story unrelatedto social skills, 15/15

Quality: Fair

G1: 9.49 2.09G2: 10.33 2.53G3: 8.85 1.59

G1: 86.2 22.8G2: 81.00 20.26G3: 79.47 22.68

G1 & G2 showed significant game play skillimprovements across four trials while G3 did not(p


76/906

42

Table 11. Outcomes of RCTs of social skills behavioral interventions (continued) Author , year, cou ntry


Study quality

Age, mean years SDIQ, mean SD

Key outcomes

Frankel et al. 1 1 2010, US

G1: Childrens FriendshipTraining, 35/26G2: Delayed TreatmentControl group, 33/31

Quality: Fair

G1: 8.6 1.27G2: 8.46 1.25

G1: 106.9 19.1G2: 100.5 15.7

Parents of G1 reported that their children hostedsignificantly more play dates after treatment relative

to G2 (p


77/906

43

hyperactivity, inattention, challenging behaviors, and depression ratings. However changes oneach scale fell short of statistical significance in comparison with the control group. A second parent-focused RCT addressed the Stepping Stones Triple P Parenting Program,153,154 whichfocuses on managing childrens behavior by considering the function of the behavior and uses procedures such as descriptive praise, planned ignoring, skill acquisition, and communication.

Parents of the children in the treatment group reported statistically significant decreases inchild challenging behavior on the Eyberg Child Behavior Inventory Intensity and ProblemScales. Wait-list controls eventually received the same treatment, and parents of children in thisgroup also reported statistically significant decreases in child challenging behavior on bothEyberg Child Behavior Inventory scales. At six-month follow up, the treatment group maintainegains on both the Eyberg scales.

The additional studies in this section included three RCTs that compared the effects ofimitation and contingent responsiveness.163-165 Contingently responsive behavior refers to theadult responding to the childs initiations by either commenting back or gesturing within the placontext. In the first phase, the child entered the room with an adult present holding a neutralfacial expression. During Phase 2, the adult interacted with the child by using either imitation o

contingently responsive behavior in response to the childs behavior. The third phase mimickedPhase 1, and the fourth and final phase included a spontaneous play interaction. Each of thesefour phases was three minutes in duration.

Each of the three RCTs included 20 children randomly assigned to either the imitation groupor the contingently responsive group,163-165 Significantly greater effects were seen in theimitation group compared with the contingent responsiveness groups in all three studies.Improvements included spending more time engaged with both objects and adults,163 a greaterreduction in motor activity,165 and more social interest.164

Two RCTs,155-157one of which was fair quality,155,156 and two case series158,167focused on the potential for interventions based on joint attention or symbolic play. Generally speaking,interventions with a joint attention focus did result in improvements in tasks based on jointattention. In the first RCT,157 all groups improved in coordinated joint looks over time. Nodifferences were found in pointing to a toy or giving a toy to an adult to share in any group. BotJoint Attention and Symbolic Play groups improved in the following areas compared withcontrols: showing toys to an adult, shared looks between a toy and the childs mother, andsymbolic play skills.

Compared with other groups, the Joint Attention group showed more improvement inresponding to joint attention over time. With respect to mother-child interactions (generalizationassessing the same outcome areas, the Joint Attention group had significantly greaterimprovement than the Symbolic Play group in giving and showing a toy. Children in the JointAttention group engaged in more child-initiated joint engagement than those in the controlgroup. The Symbolic Play group showed significantly greater improvement on the StructuredPlay Assessment than did the control group for overall mastered level of play. In the secondRCT,157 significantly more children in the Joint Attention group engaged in coordinated looksduring the final stimulus presentation (76.5 percent) than in the Symbolic Play group(38.9 percent). Children in the Joint Attention group engaged in significantly longer periods ofcoordinated looks between the person in the room and the stimulus presentations across the thretime periods.

A second RCT155,156 comparing joint attention and symbolic play interventions included58 children with autism between 3 and 4 years of age. Investigators assessed language


78/906

44

development, joint attention and play skills, and mother-child interactions at pre- and post-intervention and 6 and 12 months after the end of the 5 to 6 week intervention. Children in bothgroups showed significantly greater growth in expressive language, initiation of joint attention,and duration of child-initiated joint attention over time than did participants in the control group(p


79/906

45

Table 12. Outcom es of RCTs assessing pl ay-/interaction -based in terventions Author , year, c ount ry

Groups, N enrollment/ N finalStudy quality

Age, m ean SD (ran ge)IQ, mean SD

Key outcomes

Parent-focused interventionsSolomon et al. 2008, US

G1: Parent training focused onbehavior management andrequesting (PCIT), 10/10G2: Wait list, 9/9

Quality: Fair

G1: 8.2 yrs 1.7G2: 8.1 yrs 2.2

NR

Challenging behaviors decreased in bothgroups.

Scores declined on BASC Hyperactivity Scalefor G1 but not G2.

Score on BASC Adaptability Scale increasedsignificantly for G1.

Parents of G1 children reported significantlyless atypicality on the BASC scale.

Kasari et al. 1 ,1 2006, US

G1: Joint attention intervention,20/20G2: Symbolic play intervention,21/17G3: Control group, 17/16

Quality: Fair

G1: 43.2 7.05G2: 42.67 6.93G3: 41.94 4.93

NR

Children in the intervention groups showedgreater growth in expressive language,initiation of joint attention, and duration ofchild-initiated joint attention than did controlgroup children (p=


80/906

46

samples.169,176;170,171;174,175 Accounting for this potential overlap, it appears that at least fourindependent studies of CBT interventions and three independent studies of parent trainingaddress anxiety and anger in children with ASDs. All studies examining CBT treatmentsincluded children ages seven and older, with means ranging from nine to eleven years of age. Intwo studies examining CBT treatments, only children with an Asperger diagnosis were

included,169,176

while the Wood et al. RCT enrolled children with an ASD and a comorbidanxiety disorder.170,171 Parent training studies included parents of children ranging from age four to twelve with

mean ages spanning seven to nine years.172,174,175,178 In three of four parent training studies, only parents of children with Asperger syndrome were included.174,175,178 In the teacher training study,children ranged in age from two to fifteen and all had diagnoses of autistic disorder.173 Table 10summarizes additional study details. Among all studies, six were fair quality and five were poor

Summary of the literature. Among the studies assessing CBT approaches, one RCT examinedthe efficacy of a modified version of the Building Confidence CBT program for treatingcomorbid anxiety disorders (i.e., separation anxiety disorder, social phobia, or obsessive

compulsive disorder) in seven to eleven year-old children with ASDs.170,171

This was the onlyRCT in which CBT occurred at the individual level.The intervention program consisted of sixteen 90-minute weekly sessions conducted by

clinical or educational psychologists or trainees in these programs. In the first report from thestudy,170,171 anxiety symptoms were assessed by evaluators blind to treatment condition using theAnxiety Disorders Interview Schedule, Clinical Global Impression (CGI)Improvement Scale,and both parent and child versions of the Multidimensional Anxiety Scale for Children.

On the CGI, 92.9 percent of children in the intervention condition met criteria for positivetreatment response, while only 9.1 percent of children in the waitlist control group met the samecriteria; on the Anxiety Disorders Interview Schedule, 64.3 percent of children in theintervention group no longer met criteria for any anxiety disorder, whereas only 9.1 percent ofchildren in the waitlist control group lost their anxiety disorder diagnosis at post-test.

Eight of ten children from the intervention group who returned for a three-month followupdid not meet criteria for any anxiety disorder at followup. Maintenance of treatment responsewas also indicated by CGI and Multidimensional Anxiety Scale for Children scores at followupThe second report from the study171 included 58 percent of participants from the initial report(42 percent new participants), and measured effects of the intervention on autism symptomsusing the Social Responsiveness Scale. Significant group differences were observed at outcomein the Social Responsiveness Scale total score as well as the social communication, socialmotivation, and social awareness subscales, with children in the intervention group showingfewer autism symptoms post-treatment than children in the waitlist control group.

The remainder of CBT-based interventions (Table 13) were conducted in group settings ordirected toward parents. Reaven et al.26 conducted a nonrandomized trial of a 12-week CBT- based group intervention for high-functioning (i.e., IQ above 70) children ages eight to fourteenyears (mean = 11.83) with ASDs and comorbid anxiety disorders.

The authors created an original protocol,27 and treatment involved both children and their parents. Ten children received active treatment in this pilot study, while 23 served as a wait-listcontrol. Anxiety symptoms in children participating in the treatment group decreased over timewhile symptoms in the control group did not on the parent (but not child) version of the Kiddie-


81/906

47

Schedule for Affective Disorders and Schizophrenia or on the Screen for Child Anxiety andRelated Emotional Disorders.

Chalfant et al.25 examined children ages eight to thirteen years (mean = 10.8) with ASDs andone or more comorbid anxiety disorder diagnoses including separation anxiety, generalizedanxiety, social phobia, specific phobia, and panic disorder confirmed by structured clinical

interview using the Anxiety Disorders Interview Schedule. Children were randomly assigned totreatment and waitlist conditions. Treatment involved a 12-session CBT-based group therapy protocol, led by licensed clinical psychologists, with nine weekly two-hour sessions followed bthree monthly booster sessions.

The protocol for the study was based on a manualized CBT-based anxiety intervention forchildren (Cool Kids) with adaptations made to account for the learning style of children withASDs (e.g., more visual aids and structured worksheets, increased focus on relaxation andexposure, simplification and decreased emphasis on cognitive components of the treatment).Parents of children in the intervention group participated in concurrent parent groups with amanual also adapted from the Cool Kids program.

Measures were collected at baseline and at the completion of intervention (approximately

five and a half months later); clinicians administering the pre- and post-intervention measureswere the same clinicians who led treatment groups. No group differences were observed on anymeasure at baseline. However, children in the treatment group improved significantly over timewhile children on the waitlist did not in the number of anxiety disorder diagnoses present, as weas in the number of anxiety symptoms reported by children on the Childrens AutomaticThoughts Scale Internalising Scales, Revised Childrens Manifest Anxiety Scale, and SpenceChildrens Anxiety Scale, by parents in their report on the Spence Childrens Anxiety Scale Parent and the Strengths and Difficulties Questionnaire Emotional and Externalizing Scales, an by teachers using the Strengths and Difficulties Questionnaire Emotional and ExternalizingScales.

Table 13. Studies assessing int erventions targeting con diti ons commo nly associated with ASDs Aut ho r, year , countr y

Groups, N enrollm ent / Nfinal

Study quality

Age, m ean/yr s SDIQ, mean SD

Key outcomes

Reaven et al. 2009, US

G1: Active CBT, 10/10G2: Wait listNote: for children withcomorbid anxiety, 23/21

Quality: Fair

G1+G2: 11.02 1.9 G1+G2: 102.65 16.22

NR

Anxiety symptoms in G1 decreased over time,while symptoms in G2 did not (p=0.01).


82/906

48

Table 13. Studies assessing int erventions targeting con diti ons commo nly associated with ASDs(continued)

Aut ho r, year , countr yGroups, N enrollm ent / N

finalStudy quality

Age, m ean/yr s SDIQ, mean SD

Key outcomes

Wood et al. 1 ,1 1 2009, US

G1: Building confidence CBTprogram, 17/17G2: Wait list control, 23/23Quality: Fair

G1: 9.18 1.42G2 : 9.22 1.57

NR

92.9% of children in the intervention condition metcriteria for positive treatment response.

64.3% of children in G1 no longer met criteria forany anxiety disorder on the ADIS.

MASC scores were significantly lower (i.e.,reduction in anxiety) in G1 than in G2 post-test(p


83/906

49

SCAS-P=Spence Child Anxiety Scale-Parent version; SRS=Social Responsiveness Scale; SD=standard deviation; SWQ=SocialWorries Questionnaire

A series of papers examined CBT approaches delivered directly to children and via parenttraining. CBT provided by graduate students in psychology was assessed in high functioningchildren with Asperger disorder with comparisons made across two intervention conditions(child-only and parent-plus-child) and waitlist controls.169,176 Significant improvements inSpence Child Anxiety Scale-Parent scores were observed for both intervention groups on thetotal score and separation anxiety, obsessive compulsive disorder, social phobia, panic, and

Documents

Buena Guía Sobre La Efectividad de Las InterTEACER26_Autism_Report_04!14!2011